The International Conference on Malignant Lymphoma (ICML) has, since its first edition in 1981, become one of the must-attend conferences for the scientific community involved in the study and treatment of lymphoid neoplasms. During the 15th edition of the conference (15-ICML), held June 18-22, 2019, in Lugano, Switzerland, ADC Therapeutics will present three oral presentations and one poster presentation.
The presentations will cover the company’s pyrrolobenzodiazepine-based antibody-drug conjugates, which demonstrate potential for the treatment of relapsed or refractory lymphomas as single agents and in combination therapies, data on ADCT-402 (loncastuximab tesirine) and ADCT-301 (camidanlumab tesirine) have been selected for four presentations at the 15th ICML meeting.
The pyrrolo [2,1‐c] [1,4] benzodiazepines or PBDs are sequence‐selective DNA minor‐groove binding agents based on the naturally occurring anthramycin family of antitumor antibiotics. The best known member of which is anthramycin itself which was isolated from Streptomyces refuineus in 1965.
The PBD-based payload used in ADCR-402 and ADCT-301 has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death.
ADCT-402, an antibody-drug conjugate designed to target and kill CD19-expressing malignant B-cells, is being evaluated in an ongoing pivotal Phase II clinical trial in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (NCT03589469).
The investigational agent is also studied a Phase I clinical trial in combination with durvalumab (Imfinzi®; AstraZeneca) in patients with R/R DLBCL, mantle cell lymphoma or follicular lymphoma (NCT03685344).
In February 2019 ADC Therapeutics announced that the first patient has been dosed in a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of ADCT-402 in combination with Pharmacyclics’ ibrutinib (Imbruvica®;Pharmacyclics/Janssen Biotech) in patients with advanced diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL) (NCT03684694).
The drug is composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a ADC (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead.
CD19 is a clinically validated target for the treatment of B-cell malignancies.
ADCT-301, another antibody-drug conjugate being developed by ADC Therapeutics, is composed of a monoclonal antibody that binds to CD25 (HuMax®-TAC, licensed from Genmab A/S).
“We are pleased to be presenting compelling data at 15-ICML from our 183-patient Phase I clinical trial of ADCT-402 in relapsed or refractory B-cell lymphoma, including 139 patients with diffuse large B-cell lymphoma, as well as our 128-patient Phase I clinical trial of ADCT-301 in relapsed or refractory Hodgkin and non-Hodgkin lymphoma, including 77 patients with Hodgkin lymphoma,” Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics, said.
Ongoing pivotal trial
“Based on these data, ADCT-402 is now in an ongoing pivotal Phase II trial and we plan to commence a pivotal Phase II trial of ADCT-301 later this summer. In addition, new preclinical studies highlight the potential of these novel ADCs for the treatment of lymphomas as both single agents and in combination with other targeted drugs,” Feingold added.
“The data reinforce our position as a leader in the development of next generation PBD-based ADCs and the strength of our hematology franchise, which now also includes ADCT-602 in a Phase I clinical trial for acute lymphoblastic leukemia,” he concluded.
Link to Presentations
 Mantaj J, Jackson PJ, Rahman KM, Thurston DE From Anthramycin to Pyrrolobenzodiazepine (PBD)-Containing Antibody-Drug Conjugates (ADCs).Angew Chem Int Ed Engl. 2017 Jan 9;56(2):462-488. doi: 10.1002/anie.201510610. Epub 2016 Nov 15.[PubMed]